OBJECTIVE: To explore the incidence and clinical characteristics of West syndrome associated with phenylketonuria (WS-PKU) and significance of early combination therapy of low phenylalanine (PHE) diet and anticonvulsants (antiepileptic drugs, AEDs) in WS-PKU. SUBJECTS AND METHODS: Sixty-two WS-PKU patients (41 boys and 21 girls) out of 503 PKU patients were enrolled in the study. Age at PKU diagnosis varied from 4 months to 7 years old. Serum PHE levels were 20-38.5mg/dl. In the majority of cases, infantile spasms (IS) became manifest first preceding the PKU diagnosis, except eight cases in which spasms appeared after starting the diet therapy. All patients were subjected to mental and electroencephalographic (EEG) examination. Brain myelination was evaluated by using brain magnetic resonance imaging (MRI) with Staudt's standard. RESULTS: WS-PKU patients accounted for 12.3% of PKU patients. No patients who were given low PHE diet before age 3 months suffered from WS, whereas 17 out of 156 patients who started the diet between age 4 and 12 months developed WS later (10.9%), and similarly, 45 out of 283 patients who started the diet after 12 months of age developed WS later (15.9%). Moderate and severe mental retardation were noted in 58.8% of patients who received the diet before age 1 and in 84.4% of those after age 1 (P<0.05). EEG displayed hypsarrhythmia and diffuse background abnormality. MRI scans showed delayed myelination mainly in the cerebral lobes and corpus callosum and abnormal high T(2)-signal intensity (100%) in the periventricular region around anterior and posterior horns of both lateral ventricles. With the start of diet, spasms began to decrease its frequency, but relapsed frequently (78%) when no AEDs were given. Seizure relapse was significantly lower when valproic acid or nitrazepam were given concomitantly with the diet (18.2%). CONCLUSIONS: IS often occurred as the initial clinical sign of PKU. Early diagnosis of PKU and early therapy with low PHE diet seem to be highly effective in preventing WS.